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BEACH family of proteins: phylogenetic and functional analysis of six Dictyostelium BEACH proteins.

The beige and Chediak-Higashi syndrome (BEACH)-domain containing proteins constitute a new family of proteins found in all eukaryotes. The function of these proteins, which include the Chediak-Higashi syndrome (CHS) protein, Neurobeachin, LvsA, and FAN, is still poorly understood. To understand the diversity of this novel protein family, we analyzed a large array of BEACH-family protein sequences from several organisms. Comparison of all these sequences suggests that they can be classified into five distinct groups that may represent five distinct functional classes. In Dictyostelium we identified six proteins in this family, named LvsA-F, that belong to four of those classes. To test the function of these proteins in Dictyostelium we created disruption mutants in each of the lvs genes. Phenotypic analyses of these mutants indicate that LvsA is required for cytokinesis and osmoregulation and LvsB functions in lysosomal traffic. The LvsC-F proteins are not required for these or other processes such as growth and development. These results strongly support the concept that BEACH proteins from different classes have distinct cellular functions. Having six distinct BEACH proteins, Dictyostelium should be an excellent model system to dissect the molecular function of this interesting family of proteins.